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Medical Biochemistry > 2- Biosynthesis of fatty acids and regulation > Flashcards

2- Biosynthesis of fatty acids and regulation Flashcards

1
Q

What are lipids ?

A

They are the principal from of stored energy in most organism and major component of cellular membranes

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2
Q

Where dose fatty acids synthesis take place?

A

Liver, mammary gland, adipose tissue, kidney and brain

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3
Q

What is the main building block in the synthesis of fatty acids ?

A

Acetyl CoAs from carbohydrate and protein catabolism and product is palmitate at C16

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4
Q

What dose the synthesis pathway also utilize as a source of CO2 ?

A

NADPH, ATP, Mn, Biotin and HCO3

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5
Q

Where is the synthesis of fatty acids carried out ?

A

In the cytosol

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6
Q

Biosynthesis requires the participation of a three-carbon intermediate, what chemical compound is not involved in fatty acid breakdown ?

A

Malonyl-CoA

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7
Q

How many separate polypeptide subunits dose the bacterial enzyme ?

A

Three

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8
Q

What is the formula for malonyl-CoA ?

A

HCO3- + ATP + acetyl-CoA (to) ADP + Pi + malonyl-CoA

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9
Q

What are the two acetyl-CoA carboxylase ACC activators ?

A
  1. Citrate
  2. Insulin
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10
Q

What are the five acetyl-CoA carboxylase ACC inhibitors ?

A
  1. Glucagon
  2. Epinephrine
  3. cAMP
  4. AMPK
  5. Palmitoyl-CoA
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11
Q

What allosterically activates Acetyl-CoA Carboxylase ?

A

Citrate

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12
Q

What happens to excess acetyl-CoA ?

A

It is converted via malonyl-CoA to fatty acid for storage .

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13
Q

When is cAMP cascade activated by glucagon and epinephrine ?

A

When blood glucose is low .

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14
Q

In cAMP activation by glucagon and epinephrine what also may be phosphorylated ?

A

Acetyl-CoA carboxylase via cAMP-dependent protein kinase .

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15
Q

What will happen when the carboxylase is inhibited ?

A

Acetyle-CoA remains avilable for synthesis of ketone bodies.

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16
Q

What are the two reactions for the synthesis of fatty acid from acetyl-CoA and malonl-CoA ?

A

1- in Bacteria it is catalyzed by 6 different enzymes plus a separate acyl carrier protein.

2-in mammals it is catalyzed by individual domains of a very large polypeptide that includes an acyl carrier protein

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17
Q

What is the role of NADPH and what produces it ?

A

It serves as an electron donor in the two reactions involving substrate reduction and it it is produced mainly by pentose phosphate pathway (PPP) .

18
Q

What are the two the fatty acid synthase prosthetic groups ?

A

1- the thiol of the side chain of a cysteine residue of condensing enzyme domain.
2- the thiol of the phosphopantetheine .

19
Q

What is the fatty acid synthase ?

A

It is the system that catalyze the long carbon chains of the fatty acids .

20
Q

In the mammalian fatty acid synthase where is the active site for each enzyme found ?

A

It is found in a separate domain within a large polypeptide .

21
Q

In the mammalian fatty acid how is the intermediate remain covalently attached ?

A

As thioesters to one or two thiol groups

22
Q

What is palmitate ?

A

It is a 16-C saturated fatty acid that is the final product of fatty acid synthases reaction .

23
Q

What is the overall reaction for palmitate

A

8 acetyl-CoA + 14 NADPH + 14 H+ + 7 ATP →
palmitate + 14 NADP+ + 8 CoA + 7 ADP + 7 P; + 6H20

24
Q

How dose fatty acid synthesis occur in the cytosol ?

A

Acetyl-CoA generated in mitochondria is transported in mechanism involving citrate .

25
Q

What are the 4 main enzymes (sources) that are used in fatty acid synthesis ?

A

1- Glucose-6-phosphate dehydrogenase
2- 6-Phospogluconate dehydrogenase
3- Cytosolic isocitrate dehydrogenase
4- Malic enzyme

26
Q

What are the 3 sources of cytosolic Acetyl-CoA and reducing power for fatty acid synthesis ?

A

1- Amino acid degradation
2- Fatty acid oxidation
3- glycolysis

27
Q

How is cytosol cleaved into oxalacetate and acetyl-CoA ?

A

By a reaction catalysed by citrate lyase and it require ATP.

28
Q

What happens in the shuttle - citrate transport system ?

A

1- Malate is decarboxylated to pyruvate by malic enzyme where NADP is reduced to NADPH
2- the citrate transport system transfers the acetyl CoA from mitochondria to the cytosolic NADPH
3- malic enzyme is produced
4- the pyruvate formed enters the mitochondria.
5- pyruvae is carboxilated to form oxalacetate or converted to Acetyl CoA by aa pyruvate dehydrogenase complex reaction

29
Q

What happens to the Acetyl CoA transferred to the cytosol ?

A

It is carboxylated by acetyl CoA carboxylase using biotin as the coenzyme.

30
Q

Acetyl CoA carboxylase what is regulated ?

A

Fatty acid synthesis

31
Q

What is the difference between beta oxidation pathway and fatty acid synthesis ?

A

1- pathway location : mitochondrial matrix / cytosol.
2- acyl carriers (thiols) : Coenzyme-A / phosphopantetheine and cysteine
3- e- acceptors/donor : FAD and NAD+ / NADPH
4- -OH intermediate : L / D
5- 2-C product/ donor : acetyl-CoA / malonyl-CoA (and acetyl-CoA)

32
Q

What is the difference between fatty acid biosynthesis and degradation ?

A

1- Intermediates in fatty acid synthesis are linked covalently to the sulfhydryl (-SH) groups of special proteins, the acyl carrier proteins. In contrast, fatty acid breakdown intermediates are bound to the -SH group of coenzyme A.
2- Fatty acid synthesis occurs in the cytosol, whereas fatty acid degradation takes place in mitochondria.
3- In: animals, the enzymes of fatty acid synthesis are components of one long polypeptide chain, the fatty acid synthase, whereas no similar association exists for the degradative enzymes. (Plants and bacteria employ separate enzymes to carry out the biosynthetic reactions.)
4. The coenzyme for the oxidation-reduction reactions of fatty acid synthesis
is
NADP+/NADPH,
whereas
degradation involves the NAD+/NADH couple.

33
Q

What is the palmitate ?

A

It is the precursor of stearate, longer-chain saturated fatty acids and monounsaturated oleate and to linoleate.

34
Q

How are longer-chain of saturated fatty acids are produced ?

A

By addition of acetyl-groups

35
Q

Where are the reactions catalyzed by fatty acid elongation systems ?

A

In the smooth endoplasmic reticulum and in mitochondria

36
Q

When dose the addition of double bonds to fatty acids in eukaryotes occur?

A

Until the fatty acyl chain has reached its full length about 16 to 18 carbons

37
Q

what are the essential fatty acids for mammals obtained from dietary plant material ?

A

Linoleate and linolenate

38
Q

Where are chain elongation reactions take place ?

A

In mitochondrial and endoplasmic reticulum by addition of 2C (malonyl-CoA) units.

39
Q

What provide double bond formation to long chains of acyl-CoAs ?

A

ER systems

40
Q

How is the fatty acid chain lengthened ?

A

By adding 2-carbon units obtained from malonyl-CoA to the fatty acids activated by CoA binding each time .

41
Q

Where dose the fatty acid acyl-CoA desaturate enzymes are located ?

A

Mainly in the endoplasmic reticulum of the liver and include cyt.b5 and cyt.b5 reductase

Medical Biochemistry (5 decks)

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